反应详情

To a solution of 4-aminophenol (3.08 g, 28.2 mmol) in dichloromethane (50 ml) were added cis/trans-4-tert-butyl-cyclohexanecarbonyl chloride (11.43 g, 56.4 mmol) and pyridine (4.56 ml, 56.4 mmol), while cooling the reaction mixture in an ice bath. After the addition was completed, the cooling bath was removed and stirring was continued overnight at room temperature. The solvent was removed by evaporation and the residue was dissolved in THF (300 ml). 6N NaOH (aq, 33 ml) was added and the mixture was stirred at room temperature overnight. The organic phase was removed by evaporation. Water (200 ml) was added and the solid material collected by filtration, washed with water, dried and dissolved in methanol (100 ml). A solution of KOH (2.4 g) in methanol (50 ml) was added. After stirring for 2 h at room temperature water (200 ml) was added and the organic solvent was removed by evaporation. The aqueous phase was acidified with 1 N HCl and extracted with ethyl acetate (3×300 ml). The combined organic phases were dried and evaporated, yielding a pink oil, which was dried in vacuo. The solid material was crystallised from ethyl acetate/heptane yielding the title compound (2.03 g, 26%) as pink crystals. From the first aqueous extract a second portion of product was isolated by extraction with ethyl acetate (3×250 ml). The combined organic layers were washed with water (400 ml), saturated sodium bicarbonate (2×400 ml), dried, filtered and evaporated, yielding a pink thick oil. Crystallisation from ethyl acetate/heptane yielded a second amount of the title compound (2.75 g, 35%).

1. temperaturewhile cooling the reaction mixture in an ice bath
2. additionAfter the addition
3. customthe cooling bath was removed
4. customThe solvent was removed by evaporation
5. dissolutionthe residue was dissolved in THF (300 ml)
6. addition6N NaOH (aq, 33 ml) was added
7. stirringthe mixture was stirred at room temperature overnight
8. customThe organic phase was removed by evaporation
9. additionWater (200 ml) was added
10. filtrationthe solid material collected by filtration
11. washwashed with water
12. customdried
13. dissolutiondissolved in methanol (100 ml)
14. additionA solution of KOH (2.4 g) in methanol (50 ml) was added
15. stirringAfter stirring for 2 h at room temperature water (200 ml)
16. additionwas added
17. customthe organic solvent was removed by evaporation
18. extractionextracted with ethyl acetate (3×300 ml)
19. customThe combined organic phases were dried
20. customevaporated
21. customyielding a pink oil, which
22. customwas dried in vacuo
23. customThe solid material was crystallised from ethyl acetate/heptane yielding the title compound (2.03 g, 26%) as pink crystals
24. extractionFrom the first aqueous extract a second portion of product
25. customwas isolated by extraction with ethyl acetate (3×250 ml)
26. washThe combined organic layers were washed with water (400 ml), saturated sodium bicarbonate (2×400 ml)
27. customdried
28. filtrationfiltered
29. customevaporated
30. customyielding a pink thick oil
31. customCrystallisation from ethyl acetate/heptane